Toripalimab + Chemotherapy for Sinus Cancer

Recruiting at 1 trial location

Overseen By Glenn J Hanna, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Glenn J. Hanna

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Unresectable disease, Metastatic disease, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 6 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or high-dose corticosteroids, you may need to stop these before starting the trial.

What data supports the effectiveness of the drug combination Toripalimab + Chemotherapy for Sinus Cancer?

Research shows that docetaxel combined with cisplatin has been effective in treating head and neck cancers, with response rates of 33% to 44% and median survival of 9.6 to 11 months. Additionally, docetaxel is a potent radiosensitizer, which means it can make cancer cells more sensitive to radiation therapy, potentially improving treatment outcomes. ^{1 2 3 4 5}

Is the combination of Toripalimab, Docetaxel, and Cisplatin safe for use in humans?

Studies show that Toripalimab, when combined with Docetaxel and Cisplatin, has an acceptable safety profile in patients with advanced solid tumors, including esophageal and head and neck cancers. However, high levels of acute toxicities, such as mucositis (painful inflammation of the mouth lining) and leukopenia (low white blood cell count), have been observed, especially when Docetaxel and Cisplatin are used together. ^{3 6 7 8 9}

How is the drug Toripalimab + Chemotherapy unique for sinus cancer treatment?

Toripalimab is a unique drug because it is an immune checkpoint inhibitor that helps the immune system attack cancer cells, and when combined with chemotherapy, it may offer a new approach for treating sinus cancer, which currently lacks standard treatment options. ^{3 10 11 12 13}

What is the purpose of this trial?

The aim of this research study is to evaluate the effectiveness and safety of a combination of immunotherapy, using a drug called toripalimab, with chemotherapy drugs, Carboplatin and Docetaxel, as a possible treatment before surgery for sinonasal cancers. The names of the study drugs used in this research study are: * Toripalimab (a type of monoclonal antibody) * Carboplatin (a type of antineoplastic agent) * Docetaxel (a type of antineoplastic agent) * Cisplatin (a type of antineoplastic agent)

Research Team

Glenn J Hanna, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for individuals with certain types of sinus cancer, including squamous cell carcinoma and sinonasal tumors. Participants should be candidates for surgery and have not undergone chemotherapy or radiation therapy for their condition.

Inclusion Criteria

Participants must be willing to provide blood and tissue pre-treatment and at the time of surgery for pathologic and correlative analyses

Ability to understand and the willingness to sign a written informed consent document

My squamous cell carcinoma can be surgically removed according to my surgeon.

Exclusion Criteria

My cancer in the nasal area is not SCC or SNUC.

My condition cannot be treated with surgery.

I do not have uncontrolled HIV or active Hepatitis B/C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Toripalimab with Docetaxel and Carboplatin for 2 cycles of 21 days each, followed by surgical resection of the tumor

6 weeks

Multiple visits for drug administration and tumor assessment

Post-operative Radiation Therapy

Participants receive radiation therapy with Toripalimab every 3 weeks for up to 8 cycles, based on pathological response

24 weeks

Radiation therapy sessions and follow-up visits

Follow-up

Participants are monitored every 3 months for 1 year with imaging at 3 months

12 months

4 visits (in-person)

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Docetaxel
• Toripalimab

Trial Overview The study tests the combination of toripalimab (an immunotherapy drug) with chemotherapy agents Carboplatin and Docetaxel before surgery in patients with sinonasal cancers. It aims to assess the effectiveness and safety of this treatment regimen.

Participant Groups

Group I: Arm 3: Post Operative Radiation Therapy With or Without Chemotherapy Experimental Treatment 2 Interventions

After pathology assessment, participants with a pathological treatment response of 2 or less will be assigned standard radiation therapy with or without standard of care Cisplatin-based chemotherapy as recommended per treatment team and standard practice guidelines. -Follow up: every 3 months for 1 year. Imaging at 3 months

Group II: Arm 2: Post Operative Radiation Therapy + Toripalimab Experimental Treatment 2 Interventions

After pathology assessment, participants with a pathological treatment response of 2 will be assigned radiation therapy per standard practice guidelines and predetermined dose of Toripalimab 1x every 3 weeks for up to 8 cycles (21 day cycles). -Follow up: every 3 months for 1 year. Imaging at 3 months

Group III: Arm 1: Toripalimab and Docetaxel Plus Carboplatin (TCD) Experimental Treatment 3 Interventions

* Baseline visit with imaging * Cycles 1 and 2 (21 day cycles) * Day 1: Predetermined dose of Toripalimab 1x daily * Day 1: Chemotherapy: predetermined dose of Docetaxel 1x daily and Carboplatin 1x daily * Tumor assessment by imaging * Surgical resection of tumor

Who Is Running the Clinical Trial?

Glenn J. Hanna

Lead Sponsor

Trials

6

Recruited

160+

Coherus Biosciences, Inc.

Industry Sponsor

Trials

19

Recruited

3,700+

Findings from Research

The TP regimen (docetaxel combined with cisplatin) showed similar efficacy to the PF regimen (cisplatin combined with 5-fluorouracil) in treating nasopharyngeal carcinoma, with both regimens achieving high rates of complete remission after concurrent chemoradiotherapy.

However, the TP regimen was associated with significantly higher rates of severe neutropenia compared to the PF regimen, indicating a need for careful monitoring of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of efficacy of docetaxel combined cisplatin (TP regimen) and cisplatin combined 5-fluorouracil (PF regimen) on locally advanced nasopharyngeal carcinoma]. Xie, FY., Qi, SN., Hu, WH., et al.[2022]

The combination of docetaxel and cisplatin demonstrated a significant overall response rate of 53.7% in patients with locally advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, indicating its efficacy as a treatment option.

Despite common hematologic and non-hematologic toxicities, the treatment was generally well-tolerated, with serious adverse effects being infrequent due to the use of corticosteroid prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. Schöffski, P., Catimel, G., Planting, AS., et al.[2020]

In a study of 7 patients with advanced sinonasal squamous cell carcinoma, a modified TPF regimen combined with radiotherapy resulted in a complete response in all patients, indicating high efficacy of this treatment approach.

Despite some severe side effects like grade 4 leukopenia and neutropenia in a few patients, the overall safety profile was acceptable, with an impressive 85.7% disease-free survival rate at 60 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Study of Chemoradiotherapy Using Modified Docetaxel, Cis-diaminodichloroplatinum, and 5-Fluorouracil for Sinonasal Squamous Cell Carcinoma. Katagiri, K., Shiga, K., Saito, D., et al.[2022]

In a phase I/II trial involving 22 patients with recurrent/metastatic head and neck cancer, the combination of docetaxel and pembrolizumab showed a 22.7% overall response rate, indicating potential efficacy in this difficult-to-treat population.

The treatment was associated with manageable side effects, with myelosuppression being the most common adverse event, while serious immune-related side effects were relatively rare, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. Fuereder, T., Minichsdorfer, C., Mittlboeck, M., et al.[2023]

Docetaxel shows promising efficacy as a treatment for recurrent squamous cell cancer of the head and neck, with response rates between 33% to 44% when combined with cisplatin, and median survival times of 9.6 to 11 months.

In the neoadjuvant setting, docetaxel has demonstrated response rates greater than 90%, indicating its potential for improving disease-free and overall survival, with ongoing trials comparing its effectiveness to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of docetaxel in the management of squamous cell cancer of the head and neck. Glisson, BS.[2018]

In a phase II trial involving 20 patients with locally advanced esophageal squamous cell carcinoma (ESCC), toripalimab combined with docetaxel and cisplatin showed a promising objective response rate of 70%, indicating significant efficacy as a neoadjuvant therapy.

The treatment was found to be safe, with common adverse events including leucopenia and immune dermatitis, but no treatment-related deaths or significant delays in surgery, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a single-center, single-arm clinical trial (ESONICT-2). Gao, L., Lu, J., Zhang, P., et al.[2022]

In a study of 20 patients with locally advanced squamous cell carcinoma of the head and neck, the addition of nimotuzumab to standard TPF chemotherapy resulted in a median overall survival of 38 months, suggesting improved efficacy compared to standard treatment alone.

The treatment was well tolerated, with mostly mild side effects (grade 1/2 toxicities), indicating that nimotuzumab can be safely integrated into the chemotherapy regimen without significantly increasing adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of Nimotuzumab to Standard TPF Regimen in Locally Advanced Head and Neck Cancer: A Single Institutional Study. Koramati, SL., Sarathy, V., Varayathu, H., et al.[2022]

The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) showed a response rate of 64% in patients at dose level I and 78.3% at dose level II, indicating significant efficacy in treating squamous cell carcinoma of the head and neck (SCCHN).

The treatment was associated with manageable safety concerns, with dose-limiting toxicities including renal toxicity and nausea, and the maximum tolerated dose was reached at level II, suggesting that dose level I is safer and recommended for further testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study. Schrijvers, D., Van Herpen, C., Kerger, J., et al.[2020]

In a study of 125 patients with locoregionally advanced nasopharyngeal carcinoma, the combination of docetaxel and cisplatin during concurrent chemoradiotherapy resulted in significantly higher rates of severe acute toxicity (88%) compared to docetaxel alone (72%) and cisplatin alone (56%).

Despite the increased toxicity, the combination treatment did not lead to improved survival outcomes, as all treatment groups showed similar 3-year overall survival rates, indicating that more intense chemotherapy may not provide additional benefits in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Acute Toxicities and Efficacy of Concurrent Chemotherapy With Docetaxel Plus Cisplatin, or Docetaxel, or Cisplatin and Helical Tomotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized Single-Center Phase II Trial. Luo, Y., Cai, B., Li, B., et al.[2022]

In a phase II trial involving 25 patients with recurrent nasopharyngeal carcinoma, toripalimab combined with intensity-modulated radiotherapy (IMRT) resulted in a high overall response rate of 79.2% and disease control in 95.8% of patients at 3 months post-treatment.

The treatment was found to be tolerable, with low incidences of severe acute side effects, although some patients experienced late severe complications such as nasopharyngeal wall necrosis (28.0%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: an open-label single-arm, phase II trial. Hua, Y., You, R., Wang, Z., et al.[2022]

In a phase 2 trial involving 42 patients with unresectable locally advanced oesophageal squamous cell carcinoma, the combination of toripalimab with chemoradiotherapy resulted in a 62% complete response rate after 3 months, indicating promising efficacy for this treatment approach.

The treatment was generally well-tolerated, with a 1-year overall survival rate of 78.4% and a median duration of response of 12.1 months, although lymphopenia was a common adverse effect, affecting 86% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. Zhu, Y., Wen, J., Li, Q., et al.[2023]

Toripalimab, an immune checkpoint inhibitor, significantly improves progression-free survival and overall survival in advanced esophageal squamous cell carcinoma when combined with chemotherapy, as shown in the JUPITER-06 trial.

However, from a cost-effectiveness perspective in China, adding toripalimab to chemotherapy is not considered cost-effective unless its price is reduced by over 40%, as the incremental cost-effectiveness ratio exceeds the country's willingness-to-pay threshold.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of toripalimab plus chemotherapy for advanced esophageal squamous cell carcinoma. Xu, K., Wu, H., Zhou, C., et al.[2023]

References

1. China pubmed.ncbi.nlm.nih.gov

[Comparison of efficacy of docetaxel combined cisplatin (TP regimen) and cisplatin combined 5-fluorouracil (PF regimen) on locally advanced nasopharyngeal carcinoma]. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Preliminary Study of Chemoradiotherapy Using Modified Docetaxel, Cis-diaminodichloroplatinum, and 5-Fluorouracil for Sinonasal Squamous Cell Carcinoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

The role of docetaxel in the management of squamous cell cancer of the head and neck. [2018]

6. China pubmed.ncbi.nlm.nih.gov

Toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a single-center, single-arm clinical trial (ESONICT-2). [2022]

7. Egypt pubmed.ncbi.nlm.nih.gov

Addition of Nimotuzumab to Standard TPF Regimen in Locally Advanced Head and Neck Cancer: A Single Institutional Study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

The Acute Toxicities and Efficacy of Concurrent Chemotherapy With Docetaxel Plus Cisplatin, or Docetaxel, or Cisplatin and Helical Tomotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized Single-Center Phase II Trial. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: an open-label single-arm, phase II trial. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Induction chemotherapy for head and neck squamous cell carcinomas (SCCHN). [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of toripalimab plus chemotherapy for advanced esophageal squamous cell carcinoma. [2023]